Table 1.

Description of some of the most used cell surface antigens to study human HSPC biology for the past 30 y

Cell surface antigen/gene name	Brief characterization	Potential and/or hypothetical function(s) in human HSPCs/HSCs	Early reference(s) used to identify/select functional HSPCs/source of human tissue used
CD34	Sialomucin: type-I integral membrane protein with a short cytoplasmic domain containing 3 protein kinase phosphorylation target sites	Potentially in the rolling process on E- and/or P-selectin–expressing cells (eg, endothelial cells)51; homing; the cytoplasmic domain interacts with CrkL;52 hence, it is hypothesized that it may regulate cell shape, adhesion, and migration	Civin et al53 (BM), Katz et al54 (BM), and Andrews et al55 (BM)
CD117/KIT (c-KIT proto-oncogene; receptor tyrosine kinase)/KIT	Type III receptor tyrosine kinase Receptor for SCF Receptor activation leads to PI3K/PDK1/Akt; JAK2; SHP-1/SHP-2; and PLC signaling	Soluble SCF stimulation leads to PI3K-PDK1-Akt signaling: cell cycle regulation by inducing cell proliferation in mouse HSCs56 Membrane-bound SCF stimulation (from the mesenchymal stroma and endothelial cells): leads to PKI3-actin signaling: cell cycle regulation potentially inducing quiescency and reducing oxidative stress via Akt/nuclear FOXO3A retention in mouse HSCs57,58 Both functions may occur in human HSPCs59	Cambareri et al60 (BM) and Ashman et al61 (BM)
CD90/THY1 (Thy-1 cell surface antigen)/THY1	GPI-anchored cell surface protein Lacks transmembrane domain	No data to support a role in HSPCs Hypothesis that HSPCs may have cross talks with niche cells via integrin binding	Baum et al20 (FBM)
CD133 (prominin-1)/ PROM1	Pentaspan transmembrane glycoprotein Binds to cholesterol-containing lipid rafts	Functions of CD133 remain very elusive in many cell types as generally associated with apoptosis, differentiation, metabolism (transferrin update), and autophagy processes No data to support its role in human HSPCs, and too many associated biological processes to hypothesize its role in human HSPCs	Yin et al62 (BM and CB)
CD93/C1qRp (complement component 1Q subcomponent receptor 1)/CD93	C-type lectin transmembrane receptor Has a highly glycosylated mucin–like domain and a short cytoplasmic tail	No data to support its role in HSPCs Described to be involved in adhesion, migration, and phagocytosis in other cell types Hypothesis is that it may regulate adhesion/migration	Danet et al41 (CB)
CD143/ACE (angiotensin I converting enzyme)/ACE	Cell surface zinc metallopeptidase that hydrolyzes peptides via the removal of a dipeptide from the C-terminus Substrates include angiotensin I, bradykinin, substance P, Ac-SDKP, etc.	Could positively control cell proliferation by metabolizing Ac-SDKP and Ang-I Ac-SDKP (released from the N-terminal degradation of thymosin β4 [secreted by endothelial cells]) reduces the proliferation and clonogenicity of human CD34+HLA-DRlo HSPCs63 Ang-II and Ang1–7 (degradation product from Ang-I) promote proliferation of human CD34+ HSPCs via AT1R64,65	Jokubaitis et al66 (CB)
CD33 (sialic acid–binding immunoglobulin-like lectin 3 [Siglec-3])/CD33	Cytoplasmic domain with 1 ITIM motif and a second ITIM-like tyrosine residue	Functions of CD33 in HSPCs unknown Hypothesis is that it may regulate inflammatory/immune responses negatively through inhibitory effects on tyrosine kinase–driven signaling pathways44	Taussig et al42 (BM and CB)
CD49f (integrin subunit α 6)/ITGA6	Form heterodimers with either integrin β1 (CD29) or integrin β4 (CD104), binding α5-laminins and α3-laminins	May be involved in adhesion to BM mesenchymal stroma cells via α5-laminins interactions26 May interact with Nov/CCN3 (endothelial cells) to control stemness31	Notta et al25 (CB)
CD201/EPCR (endothelial protein C receptor)/EPCR	Enhances protein C receptor activation Modulator of PARs	May modulate the type of PAR1 responses in HSCs by regulating APC-like (HSC retention) vs thrombin-like signaling response (HSC mobilization)38	Fares et al34 (CB)
CD370 (C-type lectin domain containing 9A)/CLEC9A	Type II membrane receptor, with a single C-type lectin-like domain Intracellular domain contains a hemi-immunoreceptor tyrosine–based activation signaling motif	Functions of CD370 in HSPCs unknown; hypothesize that may regulate inflammatory signals	Belluschi et al47 (CB)
GPRC5C (G protein-coupled receptor class C group 5-member C)/GPRC5C	G protein-coupled receptor Has short extracellular N-terminus and 7-transmembrane domain motif	The binding of hyaluronic acid to GPRC5C maintains HSPCs dormant50	Zhang et al50 (BM, CB)

The list is roughly organized chronologically in accordance with their first depiction to enrich HSPCs/HSCs. FBM, fetal bone marrow; GPI, glycophosphatidylinositol; SCF, stem cell factor.